chr19-4844759-A-G

Variant names:

• chr19-4844759-A-G
• rs373776545
• NM_005817.5:c.869T>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005817.5(PLIN3):​c.869T>C​(p.Leu290Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000011 in 1,450,904 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L290R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: PLIN3 NM_005817.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.82
• Publications: 2 publications found

Genes affected

PLIN3 (HGNC:16893): (perilipin 3) Mannose 6-phophate receptors (MPRs) deliver lysosomal hydrolase from the Golgi to endosomes and then return to the Golgi complex. The protein encoded by this gene interacts with the cytoplasmic domains of both cation-independent and cation-dependent MPRs, and is required for endosome-to-Golgi transport. This protein also binds directly to the GTPase RAB9 (RAB9A), a member of the RAS oncogene family. The interaction with RAB9 has been shown to increase the affinity of this protein for its cargo. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Aug 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005817.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLIN3	NM_005817.5	MANE Select	c.869T>C	p.Leu290Pro	missense	Exon 7 of 8	NP_005808.3
	PLIN3	NM_001164189.2		c.869T>C	p.Leu290Pro	missense	Exon 7 of 8	NP_001157661.1	O60664-3
	PLIN3	NM_001164194.2		c.833T>C	p.Leu278Pro	missense	Exon 7 of 8	NP_001157666.1	O60664-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLIN3	ENST00000221957.9	TSL:1 MANE Select	c.869T>C	p.Leu290Pro	missense	Exon 7 of 8	ENSP00000221957.3	O60664-1
	PLIN3	ENST00000585479.5	TSL:1	c.869T>C	p.Leu290Pro	missense	Exon 7 of 8	ENSP00000465596.1	O60664-3
	PLIN3	ENST00000884464.1		c.869T>C	p.Leu290Pro	missense	Exon 7 of 8	ENSP00000554523.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000110 AC: 16 AN: 1450904 Hom.: 0 Cov.: 33 AF XY: 0.0000111 AC XY: 8 AN XY: 720716

African (AFR) AF: 0.00 AC: 0 AN: 33354

American (AMR) AF: 0.00 AC: 0 AN: 42742

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25654

East Asian (EAS) AF: 0.00 AC: 0 AN: 39426

South Asian (SAS) AF: 0.00 AC: 0 AN: 84152

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52668

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.0000135 AC: 15 AN: 1107174

Other (OTH) AF: 0.0000167 AC: 1 AN: 59974

GnomAD4 genome Cov.: 32

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.048	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.17	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		3.8
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Benign	0.18
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.015	D
Polyphen		1.0	D
Vest4		0.86
MVP		0.45
MPC		0.64
ClinPred		0.97	D
GERP RS		4.2
Varity_R		0.84
gMVP		0.59
Mutation Taster		=47/53	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs373776545; hg19: chr19-4844771;